Abstract
Background: ‘Lupus brain fog’ is a phenomenon of cognitive function decline in SLE patients. Premature immunosenescence in SLE was presumed to play a significant role in the mechanism of cognitive dysfunction. Aim: To prove the correlation between the terminally-differentiated CD4+CD57+, CD8+CD57+, CD4+KLRG1+, and CD8+KLRG1+ T cells & serum levels of MMP-9 with cognitive dysfunction in SLE patients. Methods: 53 women SLE were conducted to perform MMSE and MoCA-Ina tests to evaluate cognitive function. Immunosenescence was observed by measuring the terminallydifferentiated CD4+CD57+, CD8+CD57+, CD4+KLRG1+, and CD8+KLRG1+ T cells, which were measured by flowcytometry. In addition, MMP-9, an enzyme produced by terminallydifferentiated T cells, was measured using ELISA. Results: SLE patients with cognitive dysfunction based on MMSE and MoCA-Ina test had higher percentage of CD4+CD57+, CD8+CD57+, CD4+KLRG1+, CD8+KLRG1+ T cells and serum levels of MMP-9 compared to patients with normal cognitive function. CD4+CD57+, CD8+CD57+, CD4+KLRG1+, CD8+KLRG1+ T cells percentage and serum MMP-9 level showed negative correlation with both MMSE scores (r = -0.286; r = -0.447; r = -0.279; r = -0.537; r = 0,411) and MoCA-Ina scores (r = -0.454; r = -0.539; r = -0.435; r = -0.535; r = -0.648). Meanwhile, percentage of CD4+CD57+, CD8+CD57+, CD4+KLRG1+ and CD8+KLRG1+ T cells showed positive correlation with serum MMP-9 level (r = 0.292; r = 0.414; r = 0.449; r = 0.374). Conclusion: Expansion of CD4+CD57+, CD8+C57+, CD4+KLRG1+, CD8+KLRG1+ terminally differentiated T cells & increase of serum MMP-9 level are correlated with cognitive dysfunction in SLE patients
Highlights
The clinical manifestation of degeneration in Systemic Lupus Erythematosus (SLE) showed a similar profile as in the elderly population, including a cognitive function decline.[1,2,3] The cognitive dysfunction in SLE, ‘lupus brain fog’, is reported in 20-80% of SLE patients
The number of patients with a history of neuropsychiatric SLE events was significantly higher in the subjects of SLE patients with cognitive dysfunction based on the results of the Mini-Mental State Examination (MMSE) test compared to the group without cognitive dysfunction (20.8% vs. 3.4%, p = 0.047)
Recent studies have shown that the expansion of CD8+CD57+T-Cells is associated with the phenomenon of immunosenescence, and the presence of these cells is associated with inflammatory activity due to the ability to secrete pro-inflammatory cytokines, cytotoxic molecules such as granzyme and perforin, proliferate and persist for a longer period due to resistance to apoptosis, in which known as NK-like CD8+ Effector Memory T Cell.[17,18]
Summary
The clinical manifestation of degeneration in Systemic Lupus Erythematosus (SLE) showed a similar profile as in the elderly population, including a cognitive function decline.[1,2,3] The cognitive dysfunction in SLE, ‘lupus brain fog’, is reported in 20-80% of SLE patients. Kalim H, Wahono CS, Pratama MZ, et al Correlation of CD4+CD57+, CD8+CD57+, CD4+KLRG1+, CD8+KLRG1+ T-Cells Percentage and Serum MMP-9 Level with Cognitive Dysfunction among Systemic Lupus Erythematosus Patients. Kalim H, Wahono CS, Pratama MZ, et al with decreased quality of life, social participation, and increased stress, anxiety, and depression. This condition can reduce patient compliance in carrying out treatment programs, worsening the prognosis of SLE disease. Early detection and appropriate treatment of cognitive dysfunction are challenges in holistic SLE management.[4,6,7,8] the case rate is high, the specific management of cognitive dysfunction in SLE is still minimal due to limited studies that can clearly explain the causes and underlying pathophysiological mechanisms.[3,4,5]
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